Clinical significance of predominantly peripheral diabetic retinopathy: A systematic review

Background: Predominantly peripheral diabetic retinopathy detected using ultra-widefield imaging may have clinical significance beyond conventional ETDRS-field assessment. This systematic review evaluated associations between predominantly peripheral diabetic retinopathy and disease severity, progression, peripheral non-perfusion, and central retinal outcomes.

Methods: We searched Ovid MEDLINE, Scopus, CENTRAL, ProQuest and Web of Science for studies published up to 29 May 2025. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024599635). Studies evaluating predominantly peripheral lesions or peripheral non-perfusion in individuals with type 1 or type 2 diabetes were included. Quantitative peripheral non-perfusion was assessed using non-perfusion area or non-perfusion index derived from ultra-widefield angiography or optical coherence tomography angiography. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklists.

Results: Twelve of 1,482 identified studies met inclusion criteria. Predominantly peripheral lesion distribution showed heterogeneous associations with diabetic retinopathy severity. In one study, increasing diabetic retinopathy severity was independently associated with predominantly peripheral lesion presence (OR 3.16, 95% CI 2.39–4.18). Eyes with predominantly peripheral lesions demonstrated greater peripheral non-perfusion burden (non-perfusion index 0.43 vs 0.25; p = 0.011). In longitudinal cohorts, greater baseline peripheral non-perfusion was associated with subsequent diabetic retinopathy worsening (hazard ratio up to 1.14, 95% CI 1.04–1.24), while fluorescein angiography-defined predominantly peripheral lesions were associated with increased progression risk (hazard ratio 1.72, 95% CI 1.25–2.36).

Conclusion: Peripheral non-perfusion showed more consistent associations with diabetic retinopathy severity and progression than lesion distribution alone. However, evidence remains heterogeneous and predominantly cross-sectional. Standardised metrics and prospective longitudinal studies are required.